Role of circRNAs in regulating cell death in cancer: a comprehensive review.

Despite multiple diagnostic and therapeutic advances, including surgery, radiation therapy, and chemotherapy, cancer preserved its spot as a global health concern. Prompt cancer diagnosis, treatment, and prognosis depend on the discovery of new biomarkers and therapeutic strategies. Circular RNAs (circRNAs) are considered as a stable, conserved, abundant, and varied group of RNA molecules that perform multiple roles such as gene regulation. There is evidence that circRNAs interact with RNA-binding proteins, especially capturing miRNAs. An extensive amount of research has presented the substantial contribution of circRNAs in various types of cancer. To fully understand the linkage between circRNAs and cancer growth as a consequence of various cell death processes, including autophagy, ferroptosis, and apoptosis, more research is necessary. The expression of circRNAs could be controlled to limit the occurrence and growth of cancer, providing a more encouraging method of cancer treatment. Consequently, it is critical to understand how circRNAs affect various forms of cancer cell death and evaluate whether circRNAs could be used as targets to induce tumor death and increase the efficacy of chemotherapy. The current study aims to review and comprehend the effects that circular RNAs exert on cell apoptosis, autophagy, and ferroptosis in cancer to investigate potential cancer treatment targets.

Reducing metastasis ability of gastric cancer cell line by targeting MMP16 using miR-193a-5p and 5-FU.

PURPOSE: Co-administration of microRNAs and chemotherapy drugs effectively treats several cancers. The current study sought to investigate the function of matrix metalloproteinase 16 (MMP16) and miR-193a-5p in the pathogenesis of gastric cancer (GC). MATERIALS/METHODS: Sixty-five surgical patients, 15 receiving 5-fluorouracil (5-FU), provided GC and adjacent non-cancerous tissue. Following that, qPCR was used to assess the expression levels of MMP16 and miR-193a-5p in GC cells. The impact of miR-193a-5p and 5-FU administration on MMP16 mRNA expression was evaluated using qRT-PCR and Western blotting. MTT and Scratch tests were also conducted to assess their effects on cell viability and migration. Moreover, a rescue experiment using an MTT assay was performed. Using flow cytometry, the apoptotic rate was calculated. Finally, it was evaluated how MMP16 and miR-193a-5p related to the clinicopathological characteristics of the patients. RESULTS: The current study found that while MMP16 expression increased in GC patients (P<0.0001), miR-193a-5p expression significantly decreased (P<0.001). MMP16 down-regulation was another effect of miR-193a-5p replacement, particularly when 5-FU was added (P<0.01). In addition, this study found that miR-193a-5p, by concentrating on MMP16, decreased the migration of GC cells brought on by MMP16. In GC cell lines, miR-193 and 5-FU induce apoptosis, with the 5-FU being more pronounced when combined with mir-193, according to flow cytometry results. A strong correlation was also found between clinicopathological traits associated with MMP16 and miR-193a-5p. CONCLUSIONS: These findings suggest that miR-193a-5p, in conjunction with 5-FU, down-regulates MMP16 in GC, where it suppresses tumor growth.

MicroRNA as Key Players in Hepatocellular Carcinoma: Insights into Their Role in Metastasis.

Liver cancer or hepatocellular carcinoma (HCC) remains the most common cancer in global epidemiology. Both the frequency and fatality of this malignancy have shown an upward trend over recent decades. Liver cancer is a significant concern due to its propensity for both intrahepatic and extrahepatic metastasis. Liver cancer metastasis is a multifaceted process characterized by cell detachment from the bulk tumor, modulation of cellular motility and invasiveness, enhanced proliferation, avoidance of the immune system, and spread either via lymphatic or blood vessels. MicroRNAs (miRNAs) are small non-coding ribonucleic acids (RNAs) playing a crucial function in the intricate mechanisms of tumor metastasis. A number of miRNAs can either increase or reduce metastasis via several mechanisms, such as control of motility, proliferation, attack by the immune system, cancer stem cell properties, altering the microenvironment, and the epithelial-mesenchymal transition (EMT). Besides, two other types of non-coding RNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) can competitively bind to endogenous miRNAs. This competition results in the impaired ability of the miRNAs to inhibit the expression of the specific messenger RNAs (mRNAs) that are targeted. Increasing evidence has shown that the regulatory axis comprising circRNA/lncRNA-miRNA-mRNA is correlated with the regulation of HCC metastasis. This review seeks to present a thorough summary of recent research on miRNAs in HCC, and their roles in the cellular processes of EMT, invasion and migration, as well as the metastasis of malignant cells. Finally, we discuss the function of the lncRNA/circRNA-miRNA-mRNA network as a crucial modulator of carcinogenesis and the regulation of signaling pathways or genes that are relevant to the metastasis of HCC. These findings have the potential to offer valuable insight into the discovery of novel therapeutic approaches for management of liver cancer metastasis.

Epithelial-mesenchymal transition in chemoradiation-induced lung damage: Mechanisms and potential treatment approaches.

Pulmonary injury is one of the key restricting factors for the therapy of malignancies with chemotherapy or following radiotherapy for chest cancers. The lung is a sensitive organ to some severely toxic antitumor drugs, consisting of bleomycin and alkylating agents. Furthermore, treatment with radiotherapy may drive acute and late adverse impacts on the lung. The major consequences of radiotherapy and chemotherapy in the lung are pneumonitis and fibrosis. Pneumonitis may arise some months to a few years behind cancer therapy. However, fibrosis is a long-term effect that appears years after chemo/or radiotherapy. Several mechanisms such as oxidative stress and severe immune reactions are implicated in the progression of pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) is offered as a pivotal mechanism for lung fibrosis behind chemotherapy and radiotherapy. It seems that pulmonary fibrosis is the main consequence of EMT after chemo/radiotherapy. Several biological processes, consisting of the liberation of pro-inflammatory and pro-fibrosis molecules, oxidative stress, upregulation of nuclear factor of κB and Akt, epigenetic changes, and some others, may participate in EMT and pulmonary fibrosis behind cancer therapy. In this review, we aim to discuss how chemotherapy or radiotherapy may promote EMT and lung fibrosis. Furthermore, we review potential targets and effective agents to suppress EMT and lung fibrosis after cancer therapy.

Association of polyomavirus infection with lung cancer: A systematic review and meta-analysis.

AIM: The objective of this study was to investigate the pooled prevalence and possible association between polyomavirus infection and lung cancer. METHODS: A systematic publication search was conducted by identifying relevant cross-sectional and case-control studies from major online databases. Heterogeneity, OR, and corresponding 95 % CI were applied to all studies through meta-analysis and forest plot. Random effects models were used to calculate the overall pooled prevalence. Visual inspection of a funnel plot plotting the log-transformed OR and its associated standard error of the log (OR) was combined with the Begg and Egger test to examine the presence and influence of publication bias. Analyzes were performed using Stata software v.14.1. RESULTS: 23 articles (33 datasets) were included in the meta-analysis, of which 14 datasets were case/control and the rest were cross-sectional studies. The pooled polyomavirus infection rate in lung cancer patients was 0.06 % (0.02-0.11 %). In subgroup analysis, the pooled prevalence of JCV, MCPyV, KI, SV40, BKV, WU, MU, and STL was 21 %, 7 %, 6 %, 2 %, 0 %, 0 %, 0 %, and 0 % respectively. An association has been found between polyomavirus infection and lung cancer [summary OR 6.33 (95 % CI (1.76-22.77); I2=67.45 %)]. The subgroup analysis, based on the virus type, showed a strong association between MCPyV and lung cancer [summary OR 13.61 (95 % CI 2.41-76.59; I2=40.0 %)]. despite the high prevalence of JCV DNA in lung cancer tissue, analysis of case-control studies showed that JCV is not associated with lung cancer and does not increase the risk of lung cancer. CONCLUSION: This study showed a significant association between polyomaviruses infection with lung cancer. The results also revealed a pooled prevalence of 6 % for polyomaviruses in lung tumor patients. Altogether, the findings of the present work suggest that Merkel cell polyomavirus infection is a potential risk factor for lung cancer.

Targeting the pancreatic tumor microenvironment by plant-derived products and their nanoformulations.

Pancreatic cancer remains a significant health issue with limited treatment options. The tumor stroma, a complex environment made up of different cells and proteins, plays a crucial role in tumor growth and chemoresistance. Targeting tumor stroma, consisting of diverse non-tumor cells such as fibroblasts, extracellular matrix (ECM), immune cells, and also pre-vascular cells is encouraging for remodeling solid cancers, such as pancreatic cancer. Remodeling the stroma of pancreas tumors can be suggested as a strategy for reducing resistance to chemo/immunotherapy. Several studies have shown that phytochemicals from plants can affect the tumor environment and have anti-cancer properties. By targeting key pathways involved in stromal activation, phytochemicals may disrupt communication between the tumor and stroma and make tumor cells more sensitive to different treatments. Additionally, phytochemicals have immunomodulatory and anti-angiogenic properties, all of which contribute to their potential in treating pancreatic cancer. This review will provide a detailed look at how phytochemicals impact the tumor stroma and their effects on pancreatic tumor growth, spread, and response to treatment. It will also explore the potential of combining phytochemicals with other treatment options like chemotherapy, immunotherapy, and radiation.

Stealth Nanocarriers in Cancer Therapy: a Comprehensive Review of Design, Functionality, and Clinical Applications.

Nanotechnology has significantly transformed cancer treatment by introducing innovative methods for delivering drugs effectively. This literature review provided an in-depth analysis of the role of nanocarriers in cancer therapy, with a particular focus on the critical concept of the 'stealth effect.' The stealth effect refers to the ability of nanocarriers to evade the immune system and overcome physiological barriers. The review investigated the design and composition of various nanocarriers, such as liposomes, micelles, and inorganic nanoparticles, highlighting the importance of surface modifications and functionalization. The complex interaction between the immune system, opsonization, phagocytosis, and the protein corona was examined to understand the stealth effect. The review carefully evaluated strategies to enhance the stealth effect, including surface coating with polymers, biomimetic camouflage, and targeting ligands. The in vivo behavior of stealth nanocarriers and their impact on pharmacokinetics, biodistribution, and toxicity were also systematically examined. Additionally, the review presented clinical applications, case studies of approved nanocarrier-based cancer therapies, and emerging formulations in clinical trials. Future directions and obstacles in the field, such as advancements in nanocarrier engineering, personalized nanomedicine, regulatory considerations, and ethical implications, were discussed in detail. The review concluded by summarizing key findings and emphasizing the transformative potential of stealth nanocarriers in revolutionizing cancer therapy. This review enhanced the comprehension of nanocarrier-based cancer therapies and their potential impact by providing insights into advanced studies, clinical applications, and regulatory considerations.

Detailed role of SR-A1 and SR-E3 in tumor biology, progression, and therapy.

The first host defense systems are the innate immune response and the inflammatory response. Among innate immune cells, macrophages, are crucial because they preserve tissue homeostasis and eradicate infections by phagocytosis, or the ingestion of particles. Macrophages exhibit phenotypic variability contingent on their stimulation state and tissue environment and may be detected in several tissues. Meanwhile, critical inflammatory functions are played by macrophage scavenger receptors, in particular, SR-A1 (CD204) and SR-E3 (CD206), in a variety of pathophysiologic events. Such receptors, which are mainly found on the surface of multiple types of macrophages, have different effects on processes, including atherosclerosis, innate and adaptive immunity, liver and lung diseases, and, more recently, cancer. Although macrophage scavenger receptors have been demonstrated to be active across the disease spectrum, conflicting experimental findings and insufficient signaling pathways have hindered our comprehension of the molecular processes underlying its array of roles. Herein, as SR-A1 and SR-E3 functions are often binary, either protecting the host or impairing the pathophysiology of cancers has been reviewed. We will look into their function in malignancies, with an emphasis on their recently discovered function in macrophages and the possible therapeutic benefits of SR-A1 and SR-E3 targeting.

Advancing therapeutic efficacy: nanovesicular delivery systems for medicinal plant-based therapeutics.

The utilization of medicinal plant extracts in therapeutics has been hindered by various challenges, including poor bioavailability and stability issues. Nanovesicular delivery systems have emerged as promising tools to overcome these limitations by enhancing the solubility, bioavailability, and targeted delivery of bioactive compounds from medicinal plants. This review explores the applications of nanovesicular delivery systems in antibacterial and anticancer therapeutics using medicinal plant extracts. We provide an overview of the bioactive compounds present in medicinal plants and their therapeutic properties, emphasizing the challenges associated with their utilization. Various types of nanovesicular delivery systems, including liposomes, niosomes, ethosomes, and solid lipid nanoparticles, among others, are discussed in detail, along with their potential applications in combating bacterial infections and cancer. The review highlights specific examples of antibacterial and anticancer activities demonstrated by these delivery systems against a range of pathogens and cancer types. Furthermore, we address the challenges and limitations associated with the scale-up, stability, toxicity, and regulatory considerations of nanovesicular delivery systems. Finally, future perspectives are outlined, focusing on emerging technologies, integration with personalized medicine, and potential collaborations to drive forward research in this field. Overall, this review underscores the potential of nanovesicular delivery systems for enhancing the therapeutic efficacy of medicinal plant extracts in antibacterial and anticancer applications, while identifying avenues for further research and development.

Assessing the gas sensing capability of undoped and doped aluminum nitride nanotubes.

CONTEXT: CO2 and CO gas sensors are very important to recognize the insulation situation of electrical tools. ToCO explore the application of noble metal doped of aluminum nitride nanotubes for gas sensors, DFT computations according to the first principal theory were applied to study sensitivity, adsorption attributes, and electronic manner. In this investigation, platinum-doped aluminum nitride nanotubes were offered for the first time to analyze the adsorption towards CO2 and CO gases. Firm construction of platinum-doped aluminum nitride nanotubes (Pt-AlNNT) was investigated in four feasible places, and the binding energy of firm construction is 1.314 eV. Respectively, the adsorption energy between the CO2 and Pt-AlNNT systems was - 2.107 eV, while for instance of CO, the adsorption energy was - 3.258 eV. The mentioned analysis and computations are considerable for studying Pt-AlNNT as a new CO2 and CO gas sensor for electrical tools insulation. The current study revealed that the Pt-AlNNT possesses high selectivity and sensitivity towards CO2 and CO. METHODS: In this research, Pt-doped AlNNT (Pt-AlNNT) has been studied as sensing materials of CO and CO2 for the first time. The adsorption process of Pt-AlNNT has been computed and analyzed through the DFT approach. DFT computations by using B3LYP functional and 6-31 + G* basis sets have been applied in the GAMESS code for sensing attributes, which contribute to potential applications.

Critical role of miR-21/exosomal miR-21 in autophagy pathway.

Activation of autophagy, a process of cellular stress response, leads to the breakdown of proteins, organelles, and other parts of the cell in lysosomes, and can be linked to several ailments, such as cancer, neurological diseases, and rare hereditary syndromes. Thus, its regulation is very carefully monitored. Transcriptional and post-translational mechanisms domestically or in whole organisms utilized to control the autophagic activity, have been heavily researched. In modern times, microRNAs (miRNAs) are being considered to have a part in post-translational orchestration of the autophagic activity, with miR-21 as one of the best studied miRNAs, it is often more than expressed in cancer cells. This regulatory RNA is thought to play a major role in a plethora of processes and illnesses including growth, cancer, cardiovascular disease, and inflammation. Different studies have suggested that a few autophagy-oriented genes, such as PTEN, Rab11a, Atg12, SIPA1L2, and ATG5, are all targeted by miR-21, indicating its essential role in the regulation.

Dual role of mesenchymal stem/stromal cells and their cell-free extracellular vesicles in colorectal cancer.

Colorectal cancer (CRC) is one of the main causes of cancer-related deaths. However, the surgical control of the CRC progression is difficult, and in most cases, the metastasis leads to cancer-related mortality. Mesenchymal stem/stromal cells (MSCs) with potential translational applications in regenerative medicine have been widely researched for several years. MSCs could affect tumor development through secreting exosomes. The beneficial properties of stem cells are attributed to their cell-cell interactions as well as the secretion of paracrine factors in the tissue microenvironment. For several years, exosomes have been used as a cell-free therapy to regulate the fate of tumor cells in a tumor microenvironment. This review discusses the recent advances and current understanding of assessing MSC-derived exosomes for possible cell-free therapy in CRC.

Recent advances in natural nanoclay for diagnosis and therapy of cancer: A review.

Cancer is still one of the deadliest diseases, and diagnosing and treating it effectively remains difficult. As a result, advancements in earlier detection and better therapies are urgently needed. Conventional chemotherapy induces chemoresistance, has non-specific toxicity, and has a meager efficacy. Natural materials like nanosized clay mineral formations of various shapes (platy, tubular, spherical, and fibrous) with tunable physicochemical, morphological, and structural features serve as potential templates for these. As multifunctional biocompatible nanocarriers with numerous applications in cancer research, diagnosis, and therapy, their submicron size, individual morphology, high specific surface area, enhanced adsorption ability, cation exchange capacity, and multilayered organization of 0.7-1 nm thick single sheets have attracted significant interest. Kaolinite, halloysite, montmorillonite, laponite, bentonite, sepiolite, palygorskite, and allophane are the most typical nanoclay minerals explored for cancer. These multilayered minerals can function as nanocarriers to effectively carry a variety of anticancer medications to the tumor site and improve their stability, dispersibility, sustained release, and transport. Proteins and DNA/RNA can be transported using nanoclays with positive and negative surfaces. The platform for phototherapeutic agents can be nanoclays. Clays with bio-functionality have been developed using various surface engineering techniques, which could help treat cancer. The promise of nanoclays as distinctive crystalline materials with applications in cancer research, diagnostics, and therapy are examined in this review.

Deciphering the functional landscape and therapeutic implications of noncoding RNAs in the TGF-ß signaling pathway in colorectal cancer: A comprehensive review.

Colorectal cancer (CRC) remains a major global health concern, necessitating an in-depth exploration of the intricate molecular mechanisms underlying its progression and potential therapeutic interventions. Transforming Growth Factor-ß (TGF-ß) signaling, a pivotal pathway implicated in CRC plays a dual role as a tumor suppressor in the early stages and a promoter of tumor progression in later stages. Recent research has shed light on the critical involvement of noncoding RNAs (ncRNAs) in modulating the TGF-ß signaling pathway, introducing a new layer of complexity to our understanding of CRC pathogenesis. This comprehensive review synthesizes the current state of knowledge regarding the function and therapeutic potential of various classes of ncRNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), in the context of TGF-ß signaling in CRC. The intricate interplay between these ncRNAs and key components of the TGF-ß pathway is dissected, revealing regulatory networks that contribute to the dynamic balance between tumor suppression and promotion. Emphasis is placed on how dysregulation of specific ncRNAs can disrupt this delicate equilibrium, fostering CRC initiation, progression, and metastasis. Moreover, the review provides a critical appraisal of the emerging therapeutic strategies targeting ncRNAs associated with TGF-ß signaling in CRC. The potential of these ncRNAs as diagnostic and prognostic biomarkers is discussed, highlighting their clinical relevance. Additionally, the challenges and prospects of developing RNA-based therapeutics, such as RNA interference and CRISPR/Cas-based approaches, are explored in the context of modulating TGF-ß signaling for CRC treatment. In conclusion, this review offers a comprehensive overview of the intricate interplay between ncRNAs and the TGF-ß signaling pathway in CRC. By unraveling the functional significance of these regulatory elements, we gain valuable insights into the molecular landscape of CRC, paving the way for the development of novel and targeted therapeutic interventions aimed at modulating the TGF-ß signaling cascade through the manipulation of ncRNAs.

Role of microRNA-146a in cancer development by regulating apoptosis.

Despite great advances in diagnostic and treatment options for cancer, like chemotherapy surgery, and radiation therapy it continues to remain a major global health concern. Further research is necessary to find new biomarkers and possible treatment methods for cancer. MicroRNAs (miRNAs), tiny non-coding RNAs found naturally in the body, can influence the activity of several target genes. These genes are often disturbed in diseases like cancer, which perturbs functions like differentiation, cell division, cell cycle, apoptosis and proliferation. MiR-146a is a commonly and widely used miRNA that is often overexpressed in malignant tumors. The expression of miR-146a has been correlated with many pathological and physiological changes in cancer cells, such as the regulation of various cell death paths. It's been established that the control of cell death pathways has a huge influence on cancer progression. To improve our understanding of the interrelationship between miRNAs and cancer cell apoptosis, it's necessary to explore the impact of miRNAs through the alteration in their expression levels. Research has demonstrated that the appearance and spread of cancer can be mitigated by moderating the expression of certain miRNA - a commencement of treatment that presents a hopeful approach in managing cancer. Consequently, it is essential to explore the implications of miR-146a with respect to inducing different forms of tumor cell death, and evaluate its potential to serve as a target for improved chemotherapy outcomes. Through this review, we provide an outline of miR-146a's biogenesis and function, as well as its significant involvement in apoptosis. As well, we investigate the effects of exosomal miR-146a on the promotion of apoptosis in cancer cells and look into how it could possibly help combat chemotherapeutic resistance.

Natural killer cell-mediated immune surveillance in cancer: Role of tumor microenvironment.

In the immunological surveillance against cancer, natural killer (NK) cells are essential effectors that help eradicate altered cells. The complex interactions that occur between NK cells and the tumor microenvironment (TME) are thoroughly examined in this review. The review examines how cytokine stimulation affects NK cell activation, focusing on the dynamic modulation of NK cell function within the TME. It looks at NK cell-related biomarkers such as PD-1/PD-L1, methylation HOXA9 (Homeobox A9), Stroma AReactive Invasion Front Areas (SARIFA), and NKG2A/HLA-E, providing critical information about prognosis and treatment outcomes. The changing landscape of immunotherapies-including checkpoint inhibitors, CAR-NK cells, and cytokine-based interventions-is examined in the context of enhancing NK cell activity. The review highlights the potential pathways for precision medicine going forward, focusing on customized immunotherapies based on unique biomarker profiles and investigating combination medicines to produce more robust anti-tumor responses.

Recent progress and the emerging role of lncRNAs in cancer drug resistance; focusing on signaling pathways.

It is becoming more and more apparent that many of the genetic alterations associated with cancer are located in areas that do not encode proteins. lncRNAs are a class of RNAs that do not code for proteins but play a crucial role in maintaining cell function and regulating various cellular processes. By doing this, they have recently introduced what may be a brand-new and essential layer of biological control. These have more than 200 nucleotides and are linked to several diseases; as a result, they have become potential tools for therapeutic intervention. Emerging technologies suggest the presence of mutations on genomic loci that give rise to lncRNAs rather than proteins in a disease as complex as cancer. These lncRNAs play essential parts in gene regulation, which impacts several cellular homeostasis processes, including proliferation, survival, migration, and genomic stability. The leading cause of death in the world today is cancer. Delays in diagnosis and a lack of standard and efficient treatments are the leading causes of the high death rate. Clinically, surgery is frequently used successfully to remove cancers that have not spread, but it is less successful in treating metastatic cancer, which has a drastically lower chance of survival. Chemotherapeutic drugs are a typical therapy to treat the cancer that has spread to other organs. Drug resistance to chemotherapy, however, presents a significant challenge to achieving positive outcomes and is frequently the cause of treatment failure. A substantial barrier to progress in medical oncology is cancer drug resistance. Resistance can develop clinically either before or after cancer treatment. According to this study, lncRNAs influence drug resistance through several different methods. LncRNAs often impact drug resistance by controlling the expression of a few intermediary regulatory variables rather than by directly affecting drug resistance. Additionally, lncRNAs have a variety of roles in cancer medication resistance. Most lncRNAs induce drug resistance when overexpressed; however, other lncRNAs have inhibitory effects. This study provides an overview of the current understanding of lncRNAs, relevance to cancer, and potential therapeutic applications.

Mesenchymal stem cells and their extracellular vesicles in urological cancers: Prostate, bladder, and kidney.

Mesenchymal stem cells (MSCs) are recognized for their remarkable ability to differentiate into multiple cell types. They are also known to possess properties that can fight cancer, leading to attempts to modify MSCs for use in anticancer treatments. However, MSCs have also been found to participate in pathways that promote tumor growth. Many studies have been conducted to explore the potential of MSCs for clinical applications, but the results have been inconclusive, possibly due to the diverse nature of MSC populations. Furthermore, the conflicting roles of MSCs in inhibiting tumors and promoting tumor growth hinder their adaptation to anticancer therapies. Antitumorigenic and protumorigenic properties of MSCs in urological cancers such as bladder, prostate, and renal are not as well established, and data comparing them are still limited. MSCs hold significant promise as a vehicle for delivering anticancer agents and suicide genes to tumors. Presently, numerous studies have concentrated on the products derived from MSCs, such as extracellular vesicles (EVs), as a form of cell-free therapy. This work aimed to review and discuss the current knowledge of MSCs and their EVs in urological cancer therapy.

miR-199a-3p suppresses neuroinflammation by directly targeting MyD88 in a mouse model of bone cancer pain.

AIMS: Pain is a profoundly debilitating symptom in cancer patients, leading to disability, immobility, and a marked decline in their quality of life. This study aimed to investigate the potential roles of miR-199a-3p in a murine model of bone cancer pain induced by tumor cell implantation in the medullary cavity of the femur. MATERIALS AND METHODS: We assessed pain-related behaviors, including the paw withdrawal mechanical threshold (PWMT) and the number of spontaneous flinches (NSF). To investigate miRNA expression and its targets in astrocytes, we employed a combination of RNA-seq analysis, qRT-PCR, Western blotting, EdU, TUNEL, ChIP, ELISA, and luciferase reporter assays in mice (C3H/HeJ) with bone cancer pain and control groups. KEY FINDINGS: On days 10, 14, 21, and 28 post-surgery, we observed significant differences in PWTL, PWMT, and NSF when compared to the sham group (P < 0.001). qRT-PCR assays and miRNA sequencing results confirmed reduced miR-199a-3p expression in astrocytes of mice with bone cancer pain. Gain- and loss-of-function experiments demonstrated that miR-199a-3p suppressed astrocyte activation and the expression of inflammatory cytokines. In vitro investigations revealed that miR-199a-3p mimics reduced the levels of inflammatory factors in astrocytes and MyD88/NF-κB proteins. Furthermore, treatment with a miR-199a-3p agonist resulted in reduced expression of MyD88, TAK1, p-p65, and inflammatory mediators, along with decreased astrocyte activation in the spinal cord. SIGNIFICANCE: Collectively, these findings demonstrate that upregulation of miR-199a-3p may offer a therapeutic avenue for mitigating bone cancer pain in mice by suppressing neuroinflammation and inhibiting the MyD88/NF-κB signaling pathway.

Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation.

The use of nanotechnology has the potential to revolutionize the detection and treatment of cancer. Developments in protein engineering and materials science have led to the emergence of new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers for medicinal purposes have been approved for human trials, only a few have been authorized for clinical use in targeting cancer cells. In this review, we analyze some of the authorized formulations and discuss the challenges of translating findings from the lab to the clinic. This study highlights the various nanocarriers and compounds that can be used for selective tumor targeting and the inherent difficulties in cancer therapy. Nanotechnology provides a promising platform for improving cancer detection and treatment in the future, but further research is needed to overcome the current limitations in clinical translation.